On May 12, 2021 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) and CRISPR Therapeutics (Nasdaq: CRSP) reported two abstracts detailing updated data from the ongoing CTX001 clinical trials have been accepted for presentation during the European Hematology Association (EHA) (Free EHA Whitepaper) 2021 Virtual Congress (Press release, CRISPR Therapeutics, MAY 12, 2021, View Source [SID1234579776]).

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Abstract #EP736 entitled "CTX001 for Sickle Cell Disease: Safety and Efficacy Results from the Ongoing CLIMB SCD-121 Study of Autologous Crispr-Cas9-Modified CD34+ Hematopoietic Stem and Progenitor Cells," will be made available on the virtual platform as an e-poster Friday, June 11 at 9:00 CEST. The abstract posted online today includes data on patients with severe sickle cell disease with more than 3 months of follow-up, as of the interim data cut on January 28, 2021. Data will be updated and information on additional patients will be included for the congress.

Abstract #EP733 entitled "CTX001 for Transfusion-Dependent Β-Thalassemia: Safety and Efficacy Results from the Ongoing CLIMB Thal-111 Study of Autologous Crispr-Cas9-Modified CD34+ Hematopoietic Stem and Progenitor Cells," will be made available on the virtual platform as an e-poster Friday, June 11 at 9:00 CEST. The abstract posted online today includes data on patients with transfusion-dependent beta thalassemia (TDT) with more than 3 months of follow-up, including patients with the most severe genotypes, as of the interim data cut on January 21, 2021. Data will be updated and information on additional patients will be included for the congress.

The accepted abstracts are now available online on the EHA (Free EHA Whitepaper) website.

CTX001 is being investigated in two ongoing clinical trials as a potential one-time curative therapy for patients suffering from TDT and severe SCD.

About CTX001
CTX001 is an investigational, autologous, ex vivo CRISPR/Cas9 gene-edited therapy that is being evaluated for patients suffering from TDT or severe SCD, in which a patient’s hematopoietic stem cells are edited to produce high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is a form of the oxygen-carrying hemoglobin that is naturally present at birth, which then switches to the adult form of hemoglobin. The elevation of HbF by CTX001 has the potential to alleviate transfusion requirements for patients with TDT and reduce painful and debilitating sickle crises for patients with SCD. Earlier results from these ongoing trials were published as a Brief Report in The New England Journal of Medicine in January of 2021.

Based on progress in this program to date, CTX001 has been granted Regenerative Medicine Advanced Therapy (RMAT), Fast Track, Orphan Drug, and Rare Pediatric Disease designations from the U.S. Food and Drug Administration (FDA) for both TDT and SCD. CTX001 has also been granted Orphan Drug Designation from the European Commission, as well as Priority Medicines (PRIME) designation from the European Medicines Agency (EMA), for both TDT and SCD.

Among gene-editing approaches being investigated/evaluated for TDT and SCD, CTX001 is the furthest advanced in clinical development.

About CLIMB-111
The ongoing Phase 1/2 open-label trial, CLIMB-Thal-111, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with TDT. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-121
The ongoing Phase 1/2 open-label trial, CLIMB-SCD-121, is designed to assess the safety and efficacy of a single dose of CTX001 in patients ages 12 to 35 with severe SCD. The trial will enroll up to 45 patients and follow patients for approximately two years after infusion. Each patient will be asked to participate in a long-term follow-up trial.

About CLIMB-131
This is a long-term, open-label trial to evaluate the safety and efficacy of CTX001 in patients who received CTX001 in CLIMB-111 or CLIMB-121. The trial is designed to follow participants for up to 15 years after CTX001 infusion.

About the Gene-Editing Process in These Trials
Patients who enroll in these trials will have their own hematopoietic stem and progenitor cells collected from peripheral blood. The patient’s cells will be edited using the CRISPR/Cas9 technology. The edited cells, CTX001, will then be infused back into the patient as part of a stem cell transplant, a process which involves, among other things, a patient being treated with myeloablative busulfan conditioning. Patients undergoing stem cell transplants may also encounter side effects (ranging from mild to severe) that are unrelated to the administration of CTX001. Patients will initially be monitored to determine when the edited cells begin to produce mature blood cells, a process known as engraftment. After engraftment, patients will continue to be monitored to track the impact of CTX001 on multiple measures of disease and for safety.

About the Vertex-CRISPR Collaboration
Vertex and CRISPR Therapeutics entered into a strategic research collaboration in 2015 focused on the use of CRISPR/Cas9 to discover and develop potential new treatments aimed at the underlying genetic causes of human disease. CTX001 represents the first potential treatment to emerge from the joint research program. Under a recently amended collaboration agreement, Vertex will lead global development, manufacturing and commercialization of CTX001 and split program costs and profits worldwide 60/40 with CRISPR Therapeutics. This amendment is subject to customary closing conditions and clearances, including clearance under the Hart-Scott Rodino Antitrust Improvements Act.

On May 12, 2021 Context Therapeutics, a women’s oncology company developing advanced small molecule and immunotherapy treatments to transform care for hormone-driven breast and gynecological cancers, and the Sidney Kimmel Cancer Center – Jefferson Health, reported the first patient has been dosed in the Phase 2 ONWARD 221 trial in patients with metastatic endometrial cancer (Press release, Context Therapeutics, MAY 12, 2021, View Source [SID1234579775]).

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The trial, sponsored by Jefferson Health, is a clinical collaboration between Context and Jefferson Health’s Sidney Kimmel Cancer Center (SKCC) to evaluate the effect of the addition of progesterone receptor (PR) antagonist onapristone extended release (ONA-XR) to the antiestrogen, anastrozole, on outcomes for patients with metastatic endometrial cancer who have failed prior therapy. ONA-XR is an orally-administered full antagonist of the PR, a key unchecked mechanism in women’s cancers. ONA-XR is currently being evaluated in ongoing Phase 2 clinical trials in hormone-driven breast, ovarian and endometrial cancers.

"The majority of endometrial cancer patients have hormone-driven cancer. Both estrogen and progesterone drive progression in those patients, and antiestrogens, most often anastrozole, have proven, albeit limited, activity," said Russell Schilder, MD, Co-Principal Investigator and Director of the Gynecologic Medical Oncology Program at SKCC. "We will evaluate whether combining anastrozole with ONA-XR will achieve more complete hormone blockade compared with anastrozole alone, which may lead to better outcomes for patients."

The trial will enroll up to 25 patients who express the ER and/or PR biomarker (ER+ &/or PR+) and who have received prior chemotherapy treatment. The primary endpoint will be overall response rate (ORR), which is the proportion of patients who have either a complete or partial response. Secondary endpoints will include duration of response, clinical benefit rate and progression-free survival (PFS). In addition, the trial will evaluate the safety and pharmacological profile, as well as biomarker analyses to explore predictive factors of response to complete hormone blockade to inform additional ongoing Phase 2 trials of ONA-XR and a planned future Phase 3 trial.

"Context is humbled by the support and enthusiasm of Dr. Schilder and his colleagues at SKCC, one of the premier gynecologic oncology programs in the country based right here in Philadelphia," said Martin Lehr, CEO of Context Therapeutics. "Patients with advanced endometrial cancer currently have limited therapeutic options. Recent preclinical and Phase 1 data give us reason to believe ONA-XR can make a powerful addition to the current standard of care in hormone-driven endometrial cancer. Together, we look forward to exploring the potential of this combination to improve the lives of patients with this devastating disease."

About Endometrial Cancer
Endometrial cancer is the most common gynecologic malignancy in the United States with an incidence that continues to increase each year. More than 60,000 women were diagnosed with endometrial cancer in 2018 and this disease contributes to more than 10,000 deaths annually. Unopposed estrogen production and obesity are the most common risk factors for the development of endometrial cancer. The majority of patients with recurrent endometrial cancer have limited therapeutic options and the development of second-line therapies that result in improved response is an unmet clinical need.

About Onapristone Extended Release
ONA-XR (onapristone extended release) is a potent and specific antagonist of the progesterone receptor (PR) that is orally administered. Currently, there are no approved therapies that selectively target PR+ cancers. Preliminary preclinical and clinical data suggest that ONA-XR has anticancer activity by inhibiting progesterone receptor binding to chromatin, downregulating cancer stem cell mobilization and blocking immune evasion. ONA-XR is currently being evaluated in three Phase 2 clinical trials and one Phase 1b/2 clinical trial in PR+ breast, ovarian and endometrial cancers, as well as in two Phase 0 biomarker pharmacodynamic trials in breast cancer. ONA-XR is an investigational drug that has not been approved for marketing by any regulatory authority.

On May 12, 2021 Cogent Biosciences, Inc. (Nasdaq: COGT), a biotechnology company focused on developing precision therapies for genetically defined diseases, reported financial results for the first quarter ended March 31, 2021 and provided several corporate updates (Press release, Cogent Biosciences, MAY 12, 2021, View Source [SID1234579774]).

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"We are on track to initiate three clinical trials of CGT9486 this year, beginning with a study in Advanced Systemic Mastocytosis (AdvSM) patients for which we recently received IND clearance from the FDA," said Andrew Robbins, President and CEO of Cogent Biosciences. "In parallel, we continue to make great progress building a world-class R&D organization, and I’m particularly excited to welcome John and Evan to the Cogent leadership team as I know they will make tremendous contributions toward achieving our goals."

Recent Program and Corporate Highlights

Clinical Trial Evaluating CGT9486 in Patients with Advanced Systemic Mastocytosis
The US FDA recently cleared Cogent’s Investigational New Drug (IND) submission for a Phase 2 study, which remains on track for initiation in 1H 2021.
Appointed John Robinson, PhD, as Chief Scientific Officer
Dr. Robinson joins the Cogent Biosciences team from Pfizer where he most recently served as Vice President, Medicinal Chemistry. For more than 15 years prior to his time at Pfizer, Dr. Robinson was a senior member of the Array BioPharma scientific leadership team, a group responsible for developing over 25 Investigational New Drug (IND) applications including five U.S. Food and Drug Administration (FDA) approved medicines: MEKTOVI (binimetinib), TUKYSA (tucatinib), VITRAKVI (larotrectinib), Retevmo (selpercatinib) and Koselugo (selumetinib). Dr. Robinson holds a BS from Indiana University of Pennsylvania and a PhD from the University of Delaware.
Appointed Evan Kearns, JD, as Chief Legal Officer
Mr. Kearns joins Cogent with nearly 15 years of experience in the biopharmaceutical industry. Prior to joining Cogent, Mr. Kearns served as Vice President, General Counsel, Corporate Secretary and Chief Compliance Officer at Agenus Inc., where he guided the global biopharmaceutical company through multiple clinical and preclinical programs. Previously, Mr. Kearns worked at the Boston office of Goodwin Procter LLP, where he advised both public and private companies in domestic and international transactions including corporate and securities law matters, merger, acquisition and financing transactions, and corporate governance. Mr. Kearns holds a BA from Colby College and a JD from the University of Toledo.
Announced Formation of Cogent Research Team
Based in Boulder, Colorado, the Cogent Research Team will focus on pioneering best-in-class, small molecule therapeutics to expand Cogent’s pipeline and deliver novel precision therapies for patients living with unmet medical needs. Dr. John Robinson will lead the Cogent Research team composed of highly experienced scientists including several key leaders already in place.
Brad Fell as Vice President, Chemistry
Mr. Fell brings over 30 years of industrial experience in drug discovery and early clinical development to Cogent with an emphasis on oncology research. As a leader of multidisciplinary teams, Mr. Fell has managed numerous projects from target selection through candidate nomination and IND filing. Notably, he was the project leader for the Array BioPharma/Mirati Therapeutics collaboration that resulted in the KRASG12C inhibitor MRTX849 and the KRASG12D inhibitor MRTX1133. Mr. Fell holds a BS from The Ohio State University and an MS from Northeastern University.
Francis Sullivan, PhD as Vice President, Enzymology and Structural Biology
Dr. Sullivan comes most recently from Array BioPharma/Pfizer Boulder where he was senior director of enzymology/HTS and structural biology. In nearly 20 years at Array, he was involved in numerous programs that successfully advanced compounds into clinical trials. Prior to that, Dr. Sullivan was assistant director of enzymology for 12 years at Genetics Institute/Wyeth. Dr. Sullivan holds a BA from the University of Pennsylvania and a PhD from the University of Colorado.
Shannon Winski, PhD as Vice President, Pharmacology and Toxicology
Dr. Winski comes most recently from Array BioPharma/Pfizer Boulder where she led multiple drug discovery teams from early-stage lead optimization through IND candidate selection. Prior to this, she worked in the cancer biology department at OSI Pharmaceuticals (previously Gilead Sciences), primarily providing scientific support for development stage cytotoxic and targeted therapeutic candidates. Dr. Winski holds a BS and PhD from the University of Arizona.
First Quarter 2021 Summarized Financial Results

R&D Expenses: Research and development expenses were $8.2 million for the first quarter of 2021 as compared to $9.5 million for the first quarter of 2020. This decrease is primarily related to the reduction in clinical activity of legacy cell therapy clinical trials.
G&A Expenses: General and administrative expenses were $4.6 million for the first quarter of 2021 as compared to $3.7 million for the first quarter of 2020.
Net Loss: Net loss was $11.7 million for the first quarter of 2021 as compared to a net loss of $6.1 million for the first quarter of 2020.
Cash and Cash Equivalents: As of March 31, 2021, Cogent Biosciences had cash and cash equivalents of $230.7 million. We believe our cash and cash equivalents will be sufficient to fund our operating expenses and capital expenditure requirements into 2024.

On May 12, 2021 Celyad Oncology SA (Euronext & Nasdaq: CYAD), a clinical-stage biotechnology company focused on the discovery and development of chimeric antigen receptor T-cell (CAR T) therapies for cancer, reported that an abstract highlighting initial clinical data from the Phase 1 IMMUNICY-1 trial of CYAD-211 has been accepted for e-poster presentation at the upcoming European Hematology Association (EHA) (Free EHA Whitepaper) Virtual Congress 2021 (Press release, Celyad, MAY 12, 2021, View Source [SID1234579773])

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Filippo Petti, Chief Executive Officer at Celyad Oncology, commented, "We are very pleased with the initial results from the low dose cohort of our first shRNA-based allogeneic candidate, CYAD-211, which has showed preliminary signs of clinical activity, including a confirmed partial response, with no evidence of Graft-versus-Host-Disease. We are encouraged by the observed clinical activity at such a low dose level and the overall steady progress of the trial to date. Our team is intently focused on further assessing whether shRNA-mediated knockdown can generate safe, functional and clinically relevant allogeneic CAR T-cells for the treatment of cancer while offering an alternative technology platform with key advantages over gene-editing. We are excited for the opportunity to present the latest safety, clinical activity and cell kinetic data for the program next month at EHA (Free EHA Whitepaper) and look forward to future updates for the program throughout 2021 as we move towards our goal of establishing proof-of-concept for this dynamic platform."

CYAD-211 is an investigational, non-gene edited allogeneic CAR T candidate engineered to co-express a single hairpin RNA (shRNA) and a BCMA-targeting chimeric antigen receptor in development for the treatment of relapsed/refractory multiple myeloma (r/r MM). This non-gene editing technology, which does not permanently alter the genome integrity, is intended to decrease the potential safety risk associated with "off-target" genome modifications. This "All-in-One" Vector approach with one single transduction step avoids multiple genetic modifications and cost associated with additional GMP grade materials.

EHA 2021 ePoster Presentation Details:

The following abstract published today is now available on the EHA (Free EHA Whitepaper) 2021 website. Following the presentation at the meeting, the posters will be available in the Scientific Publications section of Celyad Oncology’s website.

Title: Objective response at low dose in the first-in-human IMMUNICY-1 trial evaluating non-gene edited allogeneic CYAD-211 anti-BCMA CAR T product in relapsed or refractory multiple myeloma

Presenter: Dr. Sébastien Anguille, Antwerp University Hospital (UZA), Edegem, Belgium

Topic: Gene therapy, cellular immunotherapy and vaccination—Clinical

Date and Time: e-Poster available starting Friday, June 11, 2021 at 9:00 a.m. CEST

Abstract Number: EP739

About CYAD-211

CYAD-211 is an investigational, shRNA-based allogeneic CAR T candidate for the treatment of r/r MM. CYAD-211 is engineered to co-express an anti-BCMA targeting chimeric antigen receptor and a single shRNA to knockdown the CD3zeta component of the T cell receptor complex.

About IMMUNICY-1 Phase 1 trial

The open-label, dose-escalation trial will evaluate the safety and clinical activity of CYAD-211 following cyclophosphamide and fludarabine preconditioning chemotherapy in patients with relapsed or refractory multiple myeloma. The trial will evaluate multiple dose levels of CYAD-211: 30×106, 100×106 and 300×106 cells per infusion. For more information, please visit www.clinicaltrials.gov, study identifier number NCT04613557.

On May 12, 2021 Caelum Biosciences and Alexion Pharmaceuticals, Inc. (NASDAQ:ALXN) reported that two abstracts on CAEL-101, a potentially first-in-class amyloid fibril targeted therapy, have been accepted for e-poster presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress 2021, taking place virtually from June 9 to 17, 2021 (Press release, Caelum Biosciences, MAY 12, 2021, View Source [SID1234579771]). Both presentations will include new data from the Phase 2 open-label dose escalation study evaluating the safety and tolerability of CAEL-101 in combination with standard-of-care therapy in AL amyloidosis. One will feature data studying safety and tolerability in AL amyloidosis patients treated with 1000 mg/m2 CAEL-101 in combination with cyclophosphamide-bortezomib-dexamethasone plus daratumumab. The second will include new data further supporting the selection of the 1000 mg/m2 dose for the ongoing Phase 3 study and demonstrating the possible stabilization of cardiac disease as assessed by Mayo staging.

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The abstracts accepted for e-poster presentations are listed below and are now available on the EHA (Free EHA Whitepaper) website. All e-poster presentations will be made available on the virtual congress platform on June 11, 2021 at 09:00 a.m. CEST (3:00 a.m. EDT) and will be available throughout the duration of the Congress.

Safety and Tolerability of CAEL-101 in Combination with Cyclophosphamide-Bortezomib-Dexamethasone and Daratumumab in Patients with AL Amyloidosis. Abstract #EP1017– e-poster presentation; session title: Myeloma and other monoclonal gammopathies – Clinical.

Safety and Tolerability of CAEL-101 in Patients with AL Amyloidosis in a Phase 2 Study for a Median of 38 Weeks. Abstract #EP1018 – e-poster presentation; session title: Myeloma and other monoclonal gammopathies – Clinical.

As was previously announced, the Cardiac Amyloid Reaching for Extended Survival (CARES) Phase 3 clinical program to evaluate CAEL-101 in combination with SoC therapy in AL amyloidosis has begun. Enrollment is underway in two parallel Phase 3 studies – one in patients with Mayo stage IIIa disease (ClinicalTrials.gov Identifier: NCT04512235) and one in patients with Mayo stage IIIb disease (ClinicalTrials.gov Identifier: NCT04504825) – and will collectively enroll approximately 370 patients globally. The Phase 2 program continues with the ongoing evaluation of CAEL-101 in combination with SoC therapy plus daratumumab.

About CAEL-101
CAEL-101 is a first-in-class monoclonal antibody (mAb) designed to improve organ function by reducing or eliminating amyloid deposits in the tissues and organs of patients with AL amyloidosis. The antibody is designed to bind to misfolded light chain protein and amyloid and shows binding to both kappa and lambda subtypes. In a Phase 1a/1b study, CAEL-101 demonstrated improved organ function, including cardiac and renal function, in 27 patients with relapsed and refractory AL amyloidosis who had previously not had an organ response to standard of care therapy. CAEL-101 has received Orphan Drug Designation from both the U.S. Food and Drug Administration and European Medicine Agency as a potential therapy for patients with AL amyloidosis.

About AL Amyloidosis
AL amyloidosis is a rare systemic disorder caused by an abnormality of plasma cells in the bone marrow. Misfolded immunoglobulin light chains produced by plasma cells aggregate and form fibrils that deposit in tissues and organs. This deposition can cause widespread and progressive organ damage and high mortality rates, with death most frequently occurring as a result of cardiac failure. Current standard of care includes plasma cell directed chemotherapy and autologous stem cell transplant, but these therapies do not address the organ dysfunction caused by amyloid deposition, and up to 80 percent of patients are ineligible for transplant.

AL amyloidosis is a rare disease but is the most common form of systemic amyloidosis. There are approximately 22,000 patients across the United States, France, Germany, Italy, Spain and the United Kingdom. AL amyloidosis has a one-year mortality rate of 47 percent, 76 percent of which is caused by cardiac amyloidosis.